Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses

• DOI: 10.1016/j.chom.2022.10.010
• Publication Date: 2022-11-07T15:32:40Z
• Authors: Cherrelle Dacon; Linghang Peng; Ting-Hui Lin; Courtney Tucker; Chang-Chun D. Lee; Yu Cong; Lingshu Wang; Lauren Purser; Andrew J.R. Cooper; Jazmean K. Williams; Chul-Woo Pyo; Meng Yuan; Ivan Kosik; Zhe Hu; Ming Zhao; Divya Mohan; Mary Peterson; Jeff Skinner; Saurabh Dixit; Erin Kollins; Louis Huzella; Donna Perry; Russell Byrum; Sanae Lembirik; Michael Murphy; Yi Zhang; Eun Sung Yang; Man Chen; Kwanyee Leung; Rona S. Weinberg; Amarendra Pegu; Daniel E. Geraghty; Edgar Davidson; Benjamin J. Doranz; Iyadh Douagi; Susan Moir; Jonathan W. Yewdell; Connie Schmaljohn; Peter D. Crompton; John R. Mascola; Michael R. Holbrook; David Nemazee; Ian A. Wilson; Joshua Tan
• Keywords: 0301 basic medicine; Mesocricetus; SARS-CoV-2; Correction; COVID-19; Antibodies, Monoclonal; Antibodies, Viral; Antibodies, Neutralizing; Article; Disease Outbreaks; 3. Good health; 03 medical and health sciences; Cricetinae; Spike Glycoprotein, Coronavirus; Animals

Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors bind diverse betacoronavirus spike proteins. Most targeted an S2 epitope included K814 residue and were non-neutralizing. However, 11 targeting stem helix neutralized betacoronaviruses different lineages. Eight in this group, including six broadest most potent neutralizers, encoded by IGHV1-46 IGKV3-20. Crystal structures class at 1.5-1.75-Å resolution revealed a conserved mode binding. COV89-22 SARS-CoV-2 variants concern Omicron BA.4/5 limited disease Syrian hamsters. Collectively, these findings IGHV1-46/IGKV3-20 neutralize but indicate constitute small fraction reactive antibody response after infection.